Usage
- Benidipine + Metoprolol Succinate is prescribed for the management of hypertension (high blood pressure). It is also used in the management of angina pectoris (chest pain).
- Pharmacological Classification: This combination drug falls under two classifications:
- Benidipine: Dihydropyridine Calcium Channel Blocker
- Metoprolol Succinate: Beta-1 selective adrenergic blocker
- Mechanism of Action: Benidipine blocks calcium influx into vascular smooth muscle cells, causing vasodilation (widening of blood vessels) and lowering peripheral resistance. Metoprolol succinate reduces heart rate and myocardial contractility by blocking beta-1 adrenergic receptors, thus decreasing cardiac output. The combined effect results in a significant reduction in blood pressure.
Alternate Names
- While no specific alternate generic names exist, the individual components are sometimes referred to as:
- Benidipine hydrochloride
- Metoprolol hydrogen succinate
- Brand Names: Benidipine + Metoprolol Succinate is marketed under various brand names, including Benidin M, Beniprime M, and Benipack M. The exact brand name may vary depending on the manufacturer and region.
How It Works
- Pharmacodynamics: Benidipine primarily affects peripheral blood vessels, causing vasodilation and reducing peripheral vascular resistance. Metoprolol succinate primarily affects the heart, decreasing heart rate, contractility, and cardiac output. Both actions contribute to the antihypertensive effect.
- Pharmacokinetics: Benidipine is well-absorbed orally and extensively metabolized in the liver, mainly by CYP3A4 enzymes. Metoprolol succinate is also well-absorbed and extensively metabolized in the liver, primarily by CYP2D6 enzymes. Both drugs are excreted in urine and feces.
- Mode of Action:
- Benidipine: Inhibits calcium influx through L-type calcium channels in vascular smooth muscle, leading to vasodilation.
- Metoprolol Succinate: Competitively blocks beta-1 adrenergic receptors in the heart, reducing the effects of sympathetic stimulation, thereby decreasing heart rate and contractility.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation:
- Benidipine: Calcium channel blockade.
- Metoprolol Succinate: Beta-1 adrenergic receptor blockade.
- Elimination Pathways: Both drugs are predominantly metabolized in the liver, with subsequent renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- The standard dose is usually one tablet daily, containing a specific combination of Benidipine (e.g., 4mg) and Metoprolol Succinate (e.g., 25mg or 50mg), as prescribed by the physician.
- The dosage may be adjusted based on individual patient response and tolerability.
Children:
- The safety and efficacy of Benidipine + Metoprolol Succinate in children and adolescents under 18 years of age have not been established. Its use is generally not recommended in this population.
Special Cases:
- Elderly Patients: Begin with a lower dose and titrate cautiously, monitoring for potential side effects due to age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dose adjustments may be needed. Careful monitoring of renal function is advised.
- Patients with Hepatic Dysfunction: Dose adjustments may be needed. Monitor liver function tests.
- Patients with Comorbid Conditions: Adjust dosage based on specific comorbidity and potential drug interactions. Caution is advised in patients with diabetes, as metoprolol can mask symptoms of hypoglycemia, and in patients with chronic obstructive pulmonary disease (COPD) or asthma, as metoprolol can exacerbate bronchospasm.
Clinical Use Cases
The combination of Benidipine + Metoprolol Succinate is not typically indicated for use in emergency situations, intubation, surgical procedures, mechanical ventilation, or intensive care unit (ICU) settings. For these situations, other medications may be more appropriate.
Dosage Adjustments
- Dosage adjustments should be individualized based on the patient’s response to therapy, blood pressure control, and the presence of any comorbidities or drug interactions.
- Renal or hepatic impairment may necessitate dose reduction.
- Genetic polymorphisms affecting CYP2D6 metabolism (for metoprolol) and CYP3A4 metabolism (for benidipine) may influence individual responses and require dosage adjustments.
Side Effects
Common Side Effects
- Dizziness
- Fatigue
- Headache
- Nausea
- Vomiting
- Diarrhea
- Cold hands and feet
- Peripheral edema (swelling)
Rare but Serious Side Effects
- Hypotension (low blood pressure)
- Bradycardia (slow heart rate)
- Heart block
- Bronchospasm (difficulty breathing)
- Hypoglycemia (low blood sugar)
- Allergic reactions
Long-Term Effects
- Potential long-term effects need further investigation and monitoring but may include worsening of pre-existing heart conditions if not managed appropriately.
Adverse Drug Reactions (ADR)
- Clinically significant ADRs requiring immediate intervention include severe hypotension, bradycardia, heart block, bronchospasm, and allergic reactions.
Contraindications
- Hypersensitivity to benidipine, metoprolol, or any component of the formulation.
- Cardiogenic shock.
- Severe bradycardia.
- Second- or third-degree atrioventricular block (unless a functioning pacemaker is present).
- Sick sinus syndrome.
- Severe peripheral arterial disease.
- Untreated pheochromocytoma.
- Acute heart failure.
Drug Interactions
- Other antihypertensive medications (additive hypotensive effect).
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) – may increase benidipine levels.
- CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) – may increase metoprolol levels.
- CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine) - may decrease benidipine levels.
- Digoxin (may increase digoxin levels and risk of bradycardia).
- Insulin and oral hypoglycemic agents (metoprolol may mask hypoglycemic symptoms).
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (may decrease the antihypertensive effect).
Pregnancy and Breastfeeding
- Pregnancy: Benidipine + Metoprolol Succinate should generally be avoided during pregnancy, especially in the first trimester, due to potential risks to the fetus. Consult a doctor to assess the benefits and risks.
- Breastfeeding: Metoprolol is excreted in breast milk. Benidipine excretion is not fully determined, thus, the combination should be used with caution during breastfeeding. Infants should be monitored for potential side effects such as bradycardia and hypoglycemia.
Drug Profile Summary
- Mechanism of Action: Benidipine: Calcium channel blocker (vasodilation); Metoprolol Succinate: Beta-blocker (reduces heart rate and contractility).
- Side Effects: Dizziness, fatigue, headache, nausea, hypotension, bradycardia.
- Contraindications: Hypersensitivity, severe bradycardia, heart block, cardiogenic shock, severe peripheral artery disease.
- Drug Interactions: Other antihypertensives, CYP3A4 inhibitors/inducers, CYP2D6 inhibitors, digoxin, insulin/hypoglycemics.
- Pregnancy & Breastfeeding: Consult a doctor before use.
- Dosage: Adults: One tablet daily (Benidipine 4mg/Metoprolol Succinate 25mg or 50mg), adjustable. Not recommended for children.
- Monitoring Parameters: Blood pressure, heart rate, renal and hepatic function, electrolytes.
Popular Combinations
- While Benidipine + Metoprolol Succinate itself is a combination, sometimes it might be prescribed along with a thiazide diuretic (e.g., hydrochlorothiazide) or an ACE inhibitor (e.g., ramipril) for additional blood pressure control, when deemed necessary by the physician. Close monitoring for interactions and additive effects is crucial.
Precautions
- General Precautions: Assess baseline renal and hepatic function, electrolyte levels, and cardiac status before starting therapy.
- Specific Populations:
- Pregnant Women: Avoid unless absolutely necessary.
- Breastfeeding Mothers: Use with caution. Monitor infant.
- Children & Elderly: Not recommended for children. Elderly: Start with a lower dose and titrate slowly.
- Lifestyle Considerations: Advise patients to limit alcohol intake, avoid smoking, and adopt a healthy diet and exercise regimen.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Benidipine + Metoprolol Succinate?
A: The usual starting dose is one tablet daily containing Benidipine 4mg and Metoprolol Succinate 25mg or 50mg, depending on the formulation. The dose should be adjusted based on individual patient needs and tolerability under close medical supervision.
Q2: How should Benidipine + Metoprolol Succinate be taken?
A: It should be taken orally once a day, preferably with or after a meal to enhance absorption and minimize gastrointestinal side effects.
Q3: What are the most common side effects of this combination?
A: Common side effects include dizziness, fatigue, headache, nausea, diarrhea, cold hands and feet, and peripheral edema.
Q4: What should patients do if they miss a dose?
A: If a dose is missed, take it as soon as possible unless it is almost time for the next dose. Do not double the dose.
Q5: Can Benidipine + Metoprolol Succinate be used during pregnancy or breastfeeding?
A: Its use during pregnancy is generally avoided, especially during the first trimester, and should only be considered if the benefits outweigh the potential risks to the fetus. Caution is advised during breastfeeding, and infants should be monitored for potential side effects.
Q6: Does this medication interact with other drugs?
A: Yes, it can interact with other antihypertensives, certain antidepressants, antifungals, antivirals, digoxin, and insulin or oral hypoglycemics. Provide a complete medication list to your doctor.
Q7: Are there any specific dietary restrictions while taking this medicine?
A: Patients should limit or avoid grapefruit and grapefruit juice, as it may interfere with drug metabolism and lead to increased blood pressure lowering. It is also important to avoid consuming alcohol, as it may interact with metoprolol and enhance dizziness and other side effects.
Q8: Can patients stop taking Benidipine + Metoprolol Succinate abruptly?
A: No, patients should not discontinue the medication abruptly as this may lead to rebound hypertension or other cardiovascular complications. Dosage should be gradually tapered under medical supervision.
Q9: What are the key monitoring parameters for patients on this medication?
A: Blood pressure, heart rate, and electrocardiogram (ECG) should be monitored regularly. Renal and hepatic function tests and electrolyte levels should also be evaluated periodically. Patients with diabetes should monitor their blood glucose levels carefully.
